Recent Immunosuppression, Persistently High HIV Load Predict Lymphoma Risk

Recent immunosuppression, which causes a drop in CD4 T-cell levels, and prolonged exposure to high HIV viral load are two independent predictors of non-Hodgkin’s lymphoma among people living with HIV, a recent study shows.

While these two measures also predicted the risk of diffuse large B-cell lymphoma (DLBCL) — the most common type of non-Hodgkin’s lymphoma — low CD4 count was the sole predictor for non-Hodgkin’s lymphoma in the central nervous system (CNS), and the time with high viral load was the sole predictor for Burkitt lymphoma.

The study, “Association of immunosuppression and HIV viraemia with non-Hodgkin lymphoma risk overall and by subtype in people living with HIV in Canada and the USA: a multicentre cohort study,” was published in the journal The Lancet HIV.

The incidence of non-Hodgkin’s lymphoma — particularly CNS lymphoma, DLBCL, and Burkitt lymphoma — is significantly higher among people infected with the human immunodeficiency virus (HIV) than in the general population.

Previous research has shown that a lower count of CD4 T cells — a sign of immunosuppression — and higher HIV load are linked to a higher risk for non-Hodgkin’s lymphoma.

However, these factors seem to affect specific non-Hodgkin’s lymphoma subtypes differently. For example, while immunosuppressed patients have a substantially higher risk for CNS lymphoma and DLBCL, their risk for Burkitt lymphoma is only slightly increased.

In this study, researchers aimed to examine the evolution of CD4 T-cell counts and HIV load over time to better understand how these measures could help predict the development of non-Hodgkin’s lymphoma overall and its different subtypes.

Investigators analyzed data from 102,131 people living with HIV included in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) — the largest cohort representative of HIV care in the United States and Canada — between 1996 and 2014.

Out of the initial pool of HIV patients, 712 developed non-Hodgkin’s lymphoma — 67 had CNS non-Hodgkin’s lymphoma, 358 DLBCL, 83 Burkitt lymphoma, and 204 other kinds of non-Hodgkin’s lymphoma.

Lymphoma patients were mostly males (90%), age 40 or older (65%), and had never received anti-retroviral therapies (75%).

Using actual measurements of CD4 counts and HIV load, researchers developed a model that estimated the values of the two measures in 30-day intervals — lagged by six months to avoid non-Hodgkin’s lymphoma development affecting the values of the two parameters.

The analysis showed that recent immunosuppression — i.e., low CD4 T-cell counts six months before lymphoma development — and average viral load between 3.5 years and six months before their lymphomas were the most robust and independent predictors for the overall risk of non-Hodgkin’s lymphoma.

Then, looking at the different non-Hodgkin’s lymphoma subtypes, researchers saw that both recent immunosuppression and prolonged high viral load predicted the risk for DLBCL, but that recent immunosuppression alone was enough to predict the risk for CNS lymphoma, and prolonged high viral load alone predicted Burkitt lymphoma.

Overall, these findings show that recent immunosuppression has an impact on non-Hodgkin’s lymphoma development, but mainly on the later stages of disease, while prolonged HIV infection affects disease development for the 3-year period that precedes it.

Also, the findings “add to growing evidence that the relations between immunosuppression and HIV viraemia and risk for non-Hodgkin lymphoma vary across subtypes of non-Hodgkin lymphoma, with recent immunosuppression very strongly associated with CNS non-Hodgkin lymphoma, and cumulative HIV viraemia during the period about 3–5 years to 6 months in the past very strongly associated with Burkitt lymphoma,” researchers concluded.

The results also reinforce the need for an early diagnosis of HIV and prompt delivery of anti-retroviral therapies that prevent the virus from reaching numbers that promote lymphoma.